Regulatory T cells (Tregs) are indispensable for the control of immune homeostasis and have clinical potential as a cell therapy for treating autoimmunity. Tregs can lose expression of the lineage-defining Foxp3 transcription factor and acquire effector T cell (Teff) characteristics, a process referred to as Treg plasticity. The extent and reversibility of such plasticity during immune responses remain unknown. Here, using a murine genetic fate-mapping system, we show that Treg stability is maintained even during exposure to a complex microbial/antigenic environment. Furthermore, we demonstrate that the observed plasticity of Tregs after adoptive transfer into a lymphopenic environment is a property limited to only a subset of the Treg population, with the nonconverting majority of Tregs being resistant to plasticity upon secondary stability challenge. The unstable Treg fraction is a complex mixture of phenotypically distinct Tregs, enriched for naïve and neuropilin-1-negative Tregs, and includes peripherally induced Tregs and recent thymic emigrant Tregs These results suggest that a "purging" process can be used to purify stable Tregs that are capable of robust fate retention, with potential implications for improving cell transfer therapy.The aim of this study was to determine the relationship between proliferative activity, PD-L1 status and nuclear size changes after preoperative chemoradiotherapy (CRT) and the clinical outcome in patients with superior sulcus tumours.
Proliferative activity (MIB-1) and PD-L1 status were estimated by immunohistochemistry in the tumour cells of resection specimen in a series of 33 patients with residual tumour after trimodality therapy for a sulcus superior tumour between 2005 and 2014. A morphometric analysis of both pretreatment and post-treatment tumour materials was also performed. Results were related to disease-free survival and overall survival.
Low proliferative activity (&lt;20% MIB-1) was associated with better overall survival 2-year overall survival of 73% compared with 43% and 25%, respectively, for moderate (MIB-1 20%-50%) and high (MIB-1 &gt;50%) proliferative activity (p=0.016). A negative PD-L1 status (&lt;1% positive tumour cells) was also associated with better overall survival (p=0.021). The mean nuclear size of normal lung tissue pneumocytes was significantly smaller compared with the mean nuclear size of tumour cells of the resection specimens (median difference -38.1; range -115.2 to 16.0; p&lt;0.001). The mean nuclear size of tumour cells did not differ between pretreatment biopsies and resection specimens (median difference -4.6; range -75.2 to 86.7; p=0.14). Nuclear size was not associated with survival (p=0.82).
Low proliferative activity determined by MIB-1 as well as a negative PD-L1 expression are significantly associated with better overall survival in patients with residual tumour after CRT for superior sulcus tumour.
Low proliferative activity determined by MIB-1 as well as a negative PD-L1 expression are significantly associated with better overall survival in patients with residual tumour after CRT for superior sulcus tumour.Physical activity, sedentary behaviour and sleep are potential risk factors of mental health disorders, but previous studies have not considered the dependency between these activity domains. Therefore, we examined the associations of reallocations of time among older adults' physical activity, sedentary behaviour and sleep with depressive and anxiety symptoms using compositional isotemporal substitution analyses.
We included 1943 participants (mean age 71 years, SD 9; 52% women) from the population-based Rotterdam Study. Between 2011 and 2016, we collected accelerometer data (mean duration 5.8 days, SD 0.4) on physical activity, sedentary behaviour and sleep and self-reported data on depressive symptoms and anxiety.
A reallocation of 30 min more moderate-to-vigorous physical activity was associated with a -0.55 (95% CI -1.04 to -0.06) points lower depressive symptoms score when replacing sleep and a -0.59 (95% CI -1.06 to -0.12) points lower score when replacing sedentary behaviour, but not when replacing light physical activity (-0.70, 95% CI -1.63 to 0.24). No associations were found for anxiety.
Replacing sedentary behaviour or sleep with more moderate-to-vigorous physical activity was associated with less depressive symptoms, suggesting that mainly intensive types of physical activity are important for middle-aged and older adults in relation to depressive symptoms.
Replacing sedentary behaviour or sleep with more moderate-to-vigorous physical activity was associated with less depressive symptoms, suggesting that mainly intensive types of physical activity are important for middle-aged and older adults in relation to depressive symptoms.Depression and anxiety are prevalent among women with uterine fibroids (UF). The rate of mental health diagnoses in women with UF has not been studied.
Women aged 18-50 years with diagnosed UF were identified in the Optum Clinformatics commercial insurance claims database (OptumInsight, Eden Prairie, Minnesota) from 1 May 2000 to 31 March 2020 (n=313?754) and were matched 12 on age and calendar time to women without (n=627?539). Cox proportional hazards models estimated HRs and 95% CIs between UF and diagnosed depression, anxiety and self-directed violence, adjusting for demographics and comorbidities. https://www.selleckchem.com/products/sr-4835.html Among women with diagnosed UF, the association between hysterectomy and mental health outcomes was estimated.
After adjusting for confounders, women with diagnosed UF had a higher rate of depression (HR 1.12; 95% CI 1.10 to 1.13), anxiety (HR 1.12; 95% CI 1.10 to 1.13) and self-directed violence (HR 1.46; 95% CI 1.29 to 1.64) than women without. Among women with pain symptoms and heavy menstrual bleeding, the HR comparing women with diagnosed UF to women without was 1.21 (95% CI 1.18 to 1.25) for depression, 1.18 (95% CI 1.15 to 1.21) for anxiety and 1.68 (95% CI 1.35 to 2.09) for self-directed violence. Among women with diagnosed UF, the HR comparing women who underwent a hysterectomy to women who did not was 1.22 (95% CI 1.17 to 1.27) for depression, 1.13 (95% CI 1.09 to 1.17) for anxiety and 1.86 (95% CI 1.39 to 2.49) for self-directed violence.
Rates of depression, anxiety and self-directed violence were higher among women with diagnosed UF, particularly among those who experienced pain symptoms or who underwent hysterectomy.
Rates of depression, anxiety and self-directed violence were higher among women with diagnosed UF, particularly among those who experienced pain symptoms or who underwent hysterectomy.